Sestrin Mediates Some of the Benefits of Calorie Restriction in Flies

The practice of calorie restriction reliably improves health and extends life span in near all species tested to date. Many of the pharmacological and genetic approaches to slowing aging have emerged from studies of the cellular maintenance mechanisms triggered into greater activity by calorie restriction, or the nutrient sensing mechanisms that govern initiation of the calorie restriction response. None of these approaches have yet demonstrated themselves to be any better than the actual practice of calorie restriction, and thus while scientifically interesting, are perhaps not a good point of focus for the growing longevity industry.

The health benefits of dietary restriction have long been known. Recently, it has become clear that restriction of certain food components, especially proteins and their individual building blocks, the amino acids, is more important for the organism's response to dietary restriction than general calorie reduction. On the molecular level, one particular well-known signalling pathway, named TOR pathway, is important for longevity. "We wanted to know which factor is responsible for measuring nutrients in the cell, especially amino acids, and how this factor affects the TOR pathway. We focused on a protein called Sestrin, which was suggested to sense amino acids. However, no one has ever demonstrated amino acid sensing function of Sestrin in a living being."

"Our results in flies revealed Sestrin as a novel potential anti-ageing factor. We could show that the Sestrin protein binds certain amino acids. When we inhibited this binding, the TOR signalling pathway in the flies was less active and the flies lived longer. Flies with a mutated Sestrin protein unable to bind amino acids showed improved health in the presence of a protein-rich diet."

If the researchers increased the amount of Sestrin protein in stem cells located in the fly gut, these flies lived about ten percent longer than control flies. In addition, the increased Sestrin amounts only in the gut stem cells also protected against the negative effect of a protein-rich diet. "We are curious whether the function of Sestrin in humans is similar as in flies. Experiments with mice already showed that Sestrin is required for the beneficial effects of exercise on the health of the animal. A drug that increases the activity of the Sestrin protein might therefore be in future a novel approach to slow down the ageing process."



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